1. Field of the Invention
The present invention relates to a novel protein whose expression level fluctuates in leukocytes of IgA nephropathy patients in comparison with leukocytes of healthy persons, an antibody against the protein, DNA encoding the protein, methods for detecting the protein using the antibody, mRNA and DNA using a primer comprising a complementary nucleotide sequence to the DNA, and diagnosis and treatment of IgA nephropathy.
2. Brief Description of the Background Art
IgA nephropathy is a chronic glomerulonephritis which is characterized in that an IgA immune complex considered to be originated from blood deposits in glomerulus of the kidney. In Japan, the IgA nephropathy occupies 30% or more of primary renal diseases, and is the most common renal disease. Moreover, 15 to 30% of the patients with IgA nephropathy achieve renal failure due to poor prognosis. However, since the underlying cause of IgA nephropathy is still unclear, a fundamental therapeutic method has not been found. Additionally, definite diagnosis of IgA nephropathy imposes heavy burden on patients, because the method is carried out by removing a portion of the kidney by biopsy and recognizing deposition of the IgA immune complex in mesangium by means of an immunological staining.
It has been reported that about 50% of the patients with IgA nephropathy have a high blood IgA level [Diseases of the Kidney, 5th edition (1993), Nephron, 29, 170 (1981)]. It is considered that B cells relate to the production of IgA in blood and T cells relate to the regulation of the production. Furthermore, it has been reported that the production of cytokine, such as interleukin 4, interleukin 5, interleukin 6 or TGF-xcex2 (transforming growth factor-xcex2), is high in peripheral T cells of IgA nephropathy patients in comparison with healthy persons [Clinical and Experimental Immunology, 103, 125 (1996), Kidney International, 46, 862 (1994))] and that integrin, such as VLA (very late activation)-4 and VLA-5, are strongly activated in peripheral lymphocytes of IgA nephropathy patients [Nephrology, Dialysis, Transplantation, 10, 1342 (1995)].
On the basis of these facts, it is considered that, in IgA nephropathy, excessive IgA is produced due to abnormality in the immune system, the resulting IgA immune complex in blood deposits on the glomerulus, and the complement system is activated on the deposited IgA immune complex and the like to exert influence and cause disorders of the glomerulus. However, the cause of IgA nephropathy has not yet been determined.
Elucidation of the cause of IgA nephropathy, as well as a treatment or diagnosis which can reduce a burden on patients are long-sought. The present invention provides a novel protein which has been determined to have increased expression level in leukocytes of IgA nephropathy patients, as well as an antibody against the protein, DNA encoding the protein, methods for detecting the protein using the antibody, mRNA and DNA using the oligonucleotide comprising a complementary nucleotide sequence to the DNA, and diagnostic and therapeutic agents of IgA nephropathy.
The present invention relates to a protein comprising the amino acid sequence represented by SEQ ID NO:2; DNA encoding the protein of the present invention; DNA which comprises the nucleotide sequence represented by SEQ ID NO:1; and DNA which hybridizes with the DNA comprising the above nucleotide sequence under stringent conditions. Furthermore, the present invention relates to a recombinant vector which comprises the DNA and a vector; a transformant obtained by introducing the recombinant vector into a host cell; and a process for producing the protein, comprising culturing the transformant in a medium to produce and accumulate the protein of the present invention in the culture, and recovering the protein from the resulting culture.
Moreover, the present invention relates to a method for detecting the mRNA derived from the protein of the present invention using an oligonucleotide comprising a portion of the nucleotide sequence of the DNA of the present invention or a portion of the nucleotide sequence complementary to the DNA, for example, the oligonucleotide represented by SEQ ID NO:6 or NO:7; and IgA nephropathy diagnostic agents comprising the oligonucleotide.
Also, the present invention relates to a method for inhibiting expression of the protein of the present invention using an oligonucleotide comprising a portion of the nucleotide sequence of the DNA of the present invention or a portion of the nucleotide sequence complementary to the DNA, for example, the oligonucleotide represented by SEQ ID NO:6 or NO:7; and IgA nephropathy therapeutic agents comprising the oligonucleotide.
Additionally, the present invention relates to an antibody which specifically reacts with the protein of the present invention; a method for immunologically detecting the protein of the present invention using the antibody of the present invention; and IgA nephropathy diagnostic and therapeutic agents comprising the antibody.